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Molecular Phylogeny, Classification and Evolution of Conopeptides

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Abstract

Conopeptides are toxins expressed in the venom duct of cone snails (Conoidea, Conus). These are mostly well-structured peptides and mini-proteins with high potency and selectivity for a broad range of cellular targets. In view of these properties, they are widely used as pharmacological tools and many are candidates for innovative drugs. The conopeptides are primarily classified into superfamilies according to their peptide signal sequence, a classification that is thought to reflect the evolution of the multigenic system. However, this hypothesis has never been thoroughly tested. Here we present a phylogenetic analysis of 1,364 conopeptide signal sequences extracted from GenBank. The results validate the current conopeptide superfamily classification, but also reveal several important new features. The so-called “cysteine-poor” conopeptides are revealed to be closely related to “cysteine-rich” conopeptides; with some of them sharing very similar signal sequences, suggesting that a distinction based on cysteine content and configuration is not phylogenetically relevant and does not reflect the evolutionary history of conopeptides. A given cysteine pattern or pharmacological activity can be found across different superfamilies. Furthermore, a few conopeptides from GenBank do not cluster in any of the known superfamilies, and could represent yet-undefined superfamilies. A clear phylogenetically based classification should help to disentangle the diversity of conopeptides, and could also serve as a rationale to understand the evolution of the toxins in the numerous other species of conoideans and venomous animals at large.

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Acknowledgments

We are grateful to the European Commission for financial support. This study has been performed as a part of the CONCO cone snail genome project for health (www.conco.eu) within the 6th Framework Program (LIFESCIHEALTH-6 Integrated Project LSHB-CT-2007, contract number 037592). We are also grateful to Frédérique Lisacek from the Swiss Institute of Bioinformatics for ongoing help. We would like to thank Dr Ron Hogg of OmniScience SA for editorial support.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Atheris Laboratories, Case postale 314, Bernex, 1233, Geneva, Switzerland

    N. Puillandre, D. Koua, P. Favreau & R. Stöcklin

  2. Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT, 84112, USA

    N. Puillandre & B. M. Olivera

  3. Swiss Institute of Bioinformatics, 1206, Geneva, Switzerland

    D. Koua

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  1. N. Puillandre
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Correspondence to N. Puillandre.

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239_2012_9507_MOESM1_ESM.xls

Appendix 1: List of analysed sequences with superfamily assignation, GenBank numbers, Cys-pattern, species from which the sequence originated and corresponding feeding type F: Fish-hunting species; M: Mollusc-hunting species; W: Worm-hunting species). (XLS 200 kb)

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Puillandre, N., Koua, D., Favreau, P. et al. Molecular Phylogeny, Classification and Evolution of Conopeptides. J Mol Evol 74, 297–309 (2012). https://doi.org/10.1007/s00239-012-9507-2

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